Composition

ABSTRACT

Antimicrobial composition comprising a lactam and a hydrotrope. Antimicrobial additive composition containing a lactam and a hydrotrope.

The present invention relates to an improved antimicrobial compositioncomprising a lactam.

WO 2007/085042 and WO 2004/016588 disclose lactams for antimicrobialbenefit.

Despite the prior art there remains a need for improved antimicrobialcompositions.

Accordingly, and in a first aspect of the present invention there isprovided an antimicrobial composition comprising a lactam and ahydrotrope preferably wherein the lactam is of formula (I) or (II):

In a second aspect, there is provided an antimicrobial additivecomposition containing a lactam and a hydrotrope.

Preferably the anti-microbial composition and additive compositioncontains 0.000001 to 50% wt. lactam, more preferably 0.001 to 50% wt.even more preferably 0.01 to 5% wt, most preferably 0.01-2%.

In a third aspect of the invention there is provided an antimicrobialcomposition comprising an antimicrobial additive composition of thesecond aspect.

In a fourth aspect there is provided a method for making anantimicrobial composition comprising the steps:

(i) directly mixing a lactam with a hydrotrope to form an antimicrobialadditive composition(ii) mixing the antimicrobial additive composition of (i) with anaqueous carrier.

In a fifth aspect there is provided a method for making an antimicrobialadditive composition comprising the step of directly mixing a hydrotropewith a lactam.

In a sixth aspect, the present invention provides the use of anantimicrobial composition according to the first and third aspect or anantimicrobial additive composition according to the second aspect forpreventing or disrupting microbial growth.

Preferably the antimicrobial additive composition and the method ofmaking said additive composition is substantially free of furthercomponents.

The term “substantially free” as used herein shall be understood to meanrelatively little to no amount of any content. Preferably theantimicrobial contains less than 1 wt. % more preferably less than 0.1wt. % of further components.

Preferably the aqueous carrier is suitable for use as a carrier for ahome or personal care product. Preferred personal care products includeshampoos, hair conditioners, deodorants, skin cleansing compositions andoral care products such as toothpastes and mouthwashes. Preferred homecare products are for example a hard surface cleaner or laundrycomposition.

The antimicrobial additive composition according to the invention can beused as an antimicrobial raw material where it would be diluted in afurther composition or the composition may be a consumer product theapplication of which is intended to provide antimicrobial effect to asubstrate or even as a preservative when added to a consumercomposition.

Preferably the lactam is of formula (I) or (II):

Preferably the lactam is of formula (I) or (II) wherein:

R1 and R2 are each independently selected from hydrogen, halogen, alkyl,cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryland aralalkyl; andR3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy,oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyland —C(O)CR6=CH2;R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl,heteroaryl, and arylalkyl; andR6 is selected from hydrogen and methyl; andR7 is selected from hydrogen and —C(O)CR6=CH2; and

Preferably, at least one of R4 and R5 is hydrogen; and

Preferably, at least one of R1 and R2 is selected from hetercyclyl,heteroaryl, aryl and arylalkyl; and

Preferably, R1 is hydrogen. Preferably, R3 is hydrogen. Preferably, R4is hydrogen. Preferably, R5 is hydrogen. Preferably, R6 is hydrogen; and

Preferably, R2 is aryl or aralalkyl. More preferably, R2 comprises ahalogen substituted phenyl group.

Preferably, the hydrotrope is selected from monopropylene glycol,dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester,polyoxyethylene derivatives of castor oil and ethanol.

Preferably, the hydroptrope is present at from 0.001 to 25% wt. of thecomposition.

Preferred lactams are:

-   5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295)-   5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310)-   5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted)-   methyl    2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)    (Ref. 309)-   3-Bromo-4-hexyl-5-(bromomethylene)-2(5H)-furanone (Ref. 113)-   4-(4-Trifluoromethyl)phenyl)-2(5H)-furanone (Ref. 265)-   5-Hydroxy-5-methyl-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref.    313)-   5-(Thiophenyl-3-methylene)furan-(2H)-one (Ref. 350)

The most preferred lactams are:

-   5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295)-   5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310)-   5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted)-   methyl    2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)    (Ref. 309)

Preferably, the hydrotrope is selected from monopropylene glycol,dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester,polyoxyethylene derivatives of castor oil and ethanol.

Preferably, the polyoxyethylene sorbitan fatty ester is a monoesterselected from monolaurate, monopalmitate, monostearate and monooleate.

Preferably, the polyoxyethylene sorbitan fatty ester comprises from 5 to80 oxyethylene units, more preferably from 10 to 45 and most preferably20. Examples include Polysorbates 20, 40, 60 and 80.

The most preferred polyoxyethylene sorbitan fatty ester is Polysorbate20.

Preferably, the polyoxyethylene derivative of castor oil comprises from10 to 50 oxyethylene units, more preferably from 30 to 45 and mostpreferably 40. Examples include PEG-20, 40 and 60 hydrogenated castoroil.

The most preferred polyoxyethylene derivative of castor oil is PEG-40hydrogenated castor oil.

Preferably, the composition is a home care or personal care product.

Preferred personal care products include shampoos, hair conditioners,deodorants, skin cleansing compositions and oral care products such astoothpastes and mouthwashes. Preferred home care products include a hardsurface cleaner or laundry composition.

Lactams

Suitable lactams are disclosed in WO 2007/085042 and WO 2004/016588 thecontents of which with particular regard to the manufacture of lactamsand from WO 2007/085042 the manufacture of acrylate polymers withcertain lactams associated thereto, is incorporated by reference.

For example:

EXAMPLE 1

The following data illustrates the antimicrobial efficacy of a laundrycomposition (hereinafter ‘base composition’) comprising a lactam (Ref.295 and Ref. Unsubstituted) and a hydroptrope (monopropylene glycol) butonly where hydroptrope is mixed with lactam before adding to theremainder of the composition. The test samples were as follows:

A lactam and hydroptrope onlyB lactam added directly to base formulation (which contains MPG)—nopre-mixing prior to additionC lactam pre-mixed with hydrotrope and then added to base formulationD hydrotrope only added to base formulation

Base Formulation

% % Amount activity required Component in 100 g 100 45.87 Demin Water39.05 100 4.13 Glycerol 4.13 100 7.43 Mono Propylene Glycol (with or7.43 without lactam according to BDC above) 47 2.12 NaOH 4.51 100 2.10Triethanolamine (TEA) 2.10 100 16.59 Primary Alcohol Ethoxylate (7EO)16.59 68 0.10 Optical Brightener 0.15 50 0.81 Citric Acid 1.62 97.111.06 LAS Acid 11.39 100 3.10 Fatty Acid 3.10 70 5.53 SLES 3EO 7.90 320.41 Diethylenetriamine penta(methylene 1.28 phosphonic acid) 100 0.75Liquid Protease 0.75 100.00

Test samples were diluted in sterile water to achieve a 11.5 ppm levelof lactam. Dilute solution (80 μl) was added to a S. epidermidissuspension (20 μl) of bacteria at a concentration of 8 logs in amicroplate. Growth media (100 μl tryptone soya broth) was added to eachwell of the microplate and incubated for 20 hours. Bacterial respirationwas measured every 30 minutes and the results were:

A—lactam+hydrotrope only (respiration of surviving bacteria detected˜4-5 h)B—lactam added directly to base formulation (which contains MPG)—nopre-mixing prior to addition (respiration of surviving bacteria detected4-5 hrs)C—lactam pre-mixed with hydrotrope and then added to base formulation(respiration of surviving bacteria not detected—20 hrs is max detectiontime)D—hydrotrope added to base formulation (respiration of survivingbacteria detected 3-4 hrs).

The results are shown in FIG. 1.

EXAMPLE 2

The following illustrates the broad application of the invention withinthe realm of lactams.

The example below is from data obtained when pre-blending lactams withhydrotrope before adding to the remainder of the composition, anddiluting to 11.5 ppm and 0.575 ppm in sterile water in order to assessefficacy against S. epidermidis suspension Dilute solution (80 μl) wasadded to a S. epidermidis suspension (20 μl) of bacteria at aconcentration of 8 logs in a microplate. Growth media (100 μl tryptonesoya broth) was added to each well of the microplate and incubated for20 hours. Bacterial respiration was measured every 30 minutes. Data ofthe test samples were then compared to un-treated cell suspensions(sterile water added instead of test samples) and percent inhibitioncalculated.

Result (inhibition of bacterial respiration Test versus water control)5-methylene-4-(2′-fluorophenyl)- 79.4% dihydropyrrol-2-one5-methylene-4-(4′-bromophenyl)- 82.5% dihydroprrol-2-one5-methylene-4-phenyl-1H-pyrrol-2(5H)- 82.5% one

EXAMPLE 3

The aim of this example was to investigate methods of achievingsolubility of 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref.unsubstituted) into the following above described base formulation.

An Ultrasonic mixer was used to obtain determine solubility.

We used a Hielscher UP200S (200W) Sonic Tip on batches of 5-20 ml. Wesonicated for up to 60 minutes.

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution base @ 5% 3% in Magnetic stirring ~25% of lactamClear solution with Polysorbate 1 hour solubilised. a large quantity of20 Particles visible. particles visible 3% in PEG- Magnetic stirring~25% of lactam Clear solution with 40 1 hour solubilised. a largequantity of Hydrogenated Particles visible. particles visible Castor Oil3% in Magnetic stirring No solubility — Isopentyldiol 1 hour observed.3% in MMB Magnetic stirring No solubility — 1 hour observed. 3% inMagnetic stirring No solubility — Diglycerin 1 hour observed. 3% inMagnetic stirring No solubility — Diglycerin 1 hour observed. 3% inMagnetic stirring No solubility — Pentylene 1 hour observed. Glycol 3%in Magnetic stirring No solubility — Hexylene 1 hour observed. Glycol 3%in Magnetic stirring No solubility — Hexylene 1 hour observed. Glycol 3%in PEG- Magnetic stirring ~10% of lactam Cloudy in solution 60 1 hoursolubilised. Hydrogenated Particles visible. Castor Oil 3% in Magneticstirring ~10% of lactam Cloudy and gel-like Polysorbate 1 hour, 50 C.solubilised. lumps in solution 60 Particles visible. 3% in Magneticstirring ~10% of lactam Cloudy and gel-like Polysorbate 1 hoursolubilised. lumps in solution 80 Particles visible. 3% in Magneticstirring ~5% of lactam — Dipropylene 1 hour solubilised Glycol (slightcolour change observed showing this. Particles visible. 3% in Magneticstirring ~5% of lactam Cloudy when cooled Sorbitan 1 hour, 50 C.solubilised or added to M30 Oleate (slight colour change observedshowing this. Particles visible. 3% in Magnetic stirring ~5% of lactamCloudy solution with Sisterna 1 hour solubilised large number of SP30-C(slight colour particles visible. change observed showing this.Particles visible. 3% in Magnetic stirring ~5% of lactam Hazy solutionwith Sisterna 1 hour solubilised large number of SP50-C (slight colourparticles visible. change observed showing this. Particles visible. 3%in Magnetic stirring ~5% of lactam Cloudy solution with Sisterna 1 hoursolubilised large number of SP70-C (slight colour particles visible.change observed showing this. Particles visible.

The polysorbates and Pegylated castor oil were considered suitableenough to pursue further experimentation.

Further Evaluations with Each Candidate Solubiliser

We then tested the candidate solubilisers with 1% lactam, both with 72hours high speed magnetic stirring (with held temperature of ˜500 in thecases of solubilisers that solidify alone at room temperature) and also20 minutes Sonication.

Preparation of the Lactam Solutions

In each case we incorporated the lactam powder into the solubilisers (atthe levels indicated in the below table) using high speed stirring toavoid lumps from forming. Once the powder was added, the describedmixing method (either continued high speed stirring or Ultrasonicmixing) commenced. In the cases of Sorbitan Oleate and Polysorbate-60,we applied initial heating to approx. 500 to ensure the solubiliserswere fully liquid prior to commencing addition of the lactam. Both ofthese materials are non-flowing at room temperature. PEG-40 HydrogenatedCastor required initial heating to ˜350 to ensure complete fluidityprior to commencing.

Incorporation of the Lactam Solutions into Base

The base sample provided had a 5% ‘gap’ purposely left out as space forthe lactam solution to be added. We ensured the lactam solutions werefully uniform through constant mechanical agitation (to avoid thesettling of any unsolubilised lactam material) and added them to baseusing slow speed stirring to incorporate them without generatingaeration.

Stability Testing

We conducted stability testing on all test variants that looked positive(i.e. a reasonable proportion of lactam was solubilised). We preparedsamples of the test variants in clear plastic jars and placed them atvarious temperature conditions:

-   -   Ambient temperature.    -   40 C.    -   50 C.    -   Refrigerator.    -   High light (‘shop’ window).

The aim was to observe any difference in colour, viscosity, solubilityor general physical stability. The samples were evaluated every day andcompared to the ambient temperature sample to note any changes. Allsamples were allowed to equilibrate to ambient temperature before beingevaluated.

Isopentyldiol

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% in Magnetic stirring No solubility —Isopentyldiol 72 hours observed at any stage. 1% in 20 minutes ~5% oflactam — Isopentyldiol sonication. Temp solubilised reached 60-70 C.(forced). Large number of particles visible.

3-Methoxy-3-methyl-1-butanol

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring No solubility — 72hours observed at any stage. 1% 20 minutes ~5% of lactam — sonication.Temp solubilised reached 60-70 C. (forced). Large number of particlesvisible.

Diglycerin

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring No solubility — 72hours observed at any stage. 1% 20 minutes No solubility — sonication.Temp observed. reached 60-70 C.

Pentylene Glycol

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~5% of lactam — 72hours solubilised. Large number of particles visible. 1% 20 minutes ~5%of lactam — sonication. Temp solubilised. Large reached 60-70 C. numberof particles visible.

PEG-60 Hydrogenated Castor Oil

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Polysorbate 60

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Polysorbate 80

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Sisterna SP30-C

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Sisterna SP50-C

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Sisterna SP70-C

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 1% Magnetic stirring ~25% of lactamCloudy in solution. 72 hours at 50 C. solubilised. Particles visible.Particles visible. 1% 20 minutes ~25% of lactam Cloudy in solution.sonication. Temp solubilised. Particles visible. reached 60-70 C.Particles visible.

Polysorbate 20

Observations % lactam in Observations of when added to solvent Mixingmethod solvent solution M30 @ 5% 3% Magnetic stirring ~25% of lactamClear solution with 1 hour solubilised. a large quantity of Particlesvisible. particles visible 4.2% Magnetic stirring. ~25% of lactam Clearsolution with 24 hours solubilised, a large quantity of Particlesvisible. particles visible 4.2% Magnetic stirring. ~25% of lactam Clearsolution with 24 hours. solubilised, a large quantity of Particlesvisible. particles visible Initially stirred for 2, 4 and 6 hours. Noreal changed observed during this time (all max. 25% solubilised). 4.2%20 minutes ~50% of lactam Clear solution with sonication. Tempsolubilised. a large quantity of reached 60-70 C. Particles visibleparticles visible 4.2% 60 minutes ~60-70% of lactam Clear solution withsonication. Temp solubilised. a large quantity of reached 90 C.Particles visible particles visible 2.1% 20 minutes ~90% of lactam Clearsolution. A sonication. Temp solubilised. Dark very small number reached60-70 C. colour formed of remaining unsolubilised lactam particlesvisible 2.1% 60 minutes 90% of lactam Clear solution with sonication.Temp solubilised. Some a minute number reached 90-100 C. small particlesof particles visible. visible. 4.2% Magnetic stirring. ~25% of lactamClear solution with 48 hours solubilised, a large quantity of Particlesvisible. particles visible 2.1% Magnetic stirring. ~50% of lactam Clearsolution with 24 hours solubilised, a large quantity of Particlesvisible. particles visible 2.1% Magnetic stirring. ~75% of lactam Clearsolution with 48 hours solubilised, a large quantity of Particlesvisible. particles visible 2.1% Magnetic stirring, ~50% of lactam Clearsolution with heated to 50 C. 8 solubilised, a large quantity of hours.Particles visible. particles visible 3% 20 minutes ~50% of lactam Clearsolution with sonication. Temp solubilised. a large quantity of reached60-70 C. Particles visible particles visible Observations % lactam inObservations of when added to solvent Mixing method solvent solutionbase @ 5% 3% 60 minutes ~60-70% of lactam Clear solution withsonication. Temp solubilised. a large quantity of reached 90 C.Particles visible particles visible 1% Magnetic stirring. ~75% of lactamClear solution with 24 hours solubilised, a few particles Particlesvisible. visible 1% Magnetic stirring. ~95% of lactam Clear solutionwith 72 hours solubilised A few a few particles particles visible.visible After 48 hours it was approx. 80- 85%. 2.1% Magnetic stirring,~75% of lactam Clear solution with heated to 50 C. 72 solubilised, alarge quantity of hours. Particles visible. particles visible 1.5%Magnetic stirring. ~50% of lactam Clear solution with 48 hourssolubilised, a large quantity of Particles visible. particles visible1.5 Magnetic stirring, ~75% of lactam Clear solution with heated to 50C. 72 solubilised, a large quantity of hours. Particles visible.particles visible 1.5% 20 minutes ~75% of lactam Clear solution withsonication. Temp solubilised. Some a number of reached 60-70 C.Particles visible particles visible 1.5% 60 minutes ~95% of lactam Clearsolution with sonication. Temp solubilised. a minute number reached80-90 C. Particles visible. of particles visible Dark brown colour. 2.1%60 minutes 90% of lactam Clear solution with sonication. Tempsolubilised. Some a minute number reached 80 C. small particles ofparticles visible. visible.

PEG-40 Hydrogenated Castor Oil

Observations % lactam Observations of when added to in solvent Mixingmethod solvent solution M30 @ 5% 3% Magnetic stirring ~25% of lactamClear solution with 1 hour solubilised. a large quantity of Particlesvisible. particles visible 4.2% Magnetic stirring. ~25% of lactam Clearsolution with 24 hours solubilised, a large quantity of Particlesvisible. particles visible 4.2% Magnetic stirring. ~25% of lactam Clearsolution with 24 hours. solubilised, a large quantity of Particlesvisible. particles visible Initially stirred for 2, 4 and 6 hours. Noreal changed observed during this time (all max. 25% solubilised). 4.2%Magnetic stirring. ~25% of lactam Clear solution with 48 hourssolubilised, a large quantity of Particles visible. particles visible2.1% Magnetic stirring. ~50% of lactam Clear solution with 24 hourssolubilised, a large quantity of Particles visible. particles visible2.1% Magnetic stirring. ~75% of lactam Clear solution with 48 hourssolubilised, a large quantity of Particles visible. particles visible4.2% 20 minutes 50% of lactam Clear solution with sonication. Tempsolubilised. Large a large number of reached 60-70 C. number ofparticles visible particles visible. Very dark colour. 4.2% 60 minutes75% of lactam Some fragments sonication. Temp solubilised. Very visiblein M30, reached 110 C. dark colour. suggesting partial breakdown ofsolvent. 4.2% 60 minutes 75% of lactam Fragments sonication. Tempsolubilised. Very avoided due to reached 80 C. dark colour. temperaturecontrol. Clear solution with some small particles visible. 2.1% 20minutes 90% of lactam Clear solution with sonication. Temp appeared to asmall number of reached 80 C. solubilise however black particles smallamount of visible ‘burnt’ spots visible. 2.1% 60 minutes lactamsolubilised. Some fragments sonication. Temp Very dark colour. visiblein M30, reached 110 C. suggesting partial breakdown of solvent. 2.1%Magnetic stirring, ~50% of lactam Clear solution with heated to 50 C. 8solubilised, a large quantity of hours. Particles visible. particlesvisible 3% 20 minutes ~75% of lactam Clear solution with sonication.Temp solubilised. a large quantity of reached 60-70 C. Particles visibleparticles visible 3% 60 minutes ~75% of lactam Clear solution withsonication. Temp solubilised. a large quantity of reached 80 C.Particles visible particles visible 1% Magnetic stirring. ~75% of lactamClear solution with 24 hours solubilised, a few particles Particlesvisible. visible 1% Magnetic stirring. ~90% of lactam Clear solutionwith 72 hours solubilised, A few a few particles particles visible 1%Magnetic stirring. ~99% of lactam Clear solution with 72 hours withsolubilised, A tiny a very small temp. at 50 C. number of number ofparticles remained particles visible 2.1% 30 minutes lactam appearedClear solution with sonication. Temp to solubilise a small number ofreached 90 C. however ‘burnt’ black particles spots visible. visible

Observation and Formulation Rules Temperature and Colour Change

One of our first observations was the colour change which was visible inall successful (or partially successful) samples. We saw development ofa slight amber tinge to the solution when some lactam was starting tobecome solubilised. This colour change progressed rapidly when samplesexceeded 50 C, resulting in a dark brown colour. When the temperaturereached 65C, the dark brown colour was virtually opaque*.

*This level of temperature was only tested for the Polysorbate-20 andPEG-40 Hydrogenated Castor Oil variants.

From observations throughout the project, we concluded that ˜50 C wasthe optimum temperature for solubilising the lactam.

Mixing Conditions

Very long periods of mechanical stirring (48-72 hours) resulted inimprovements in solubilisation compared to shorter periods; however wedid not find this length of mixing to be sufficient for fullsolubilisation. Ultrasonic mixing did prove to be far more successfuland we concluded would be required for effective solubilisation,certainly with the shortlisted Polysorbate-20 and PEG-40 HydrogenatedCastor Oil candidates.

From all of the trials conducted, we believe with the right Ultrasonicmixing conditions (of energy versus batch size versus controlled max. 50C temperature), efficient solubilisation could be achieved.

1. Antimicrobial additive composition containing a lactam and ahydrotrope, wherein the hydrotrope is selected from the group consistingof monopropylene glycol, dimethylsulphoxide, polyoxyethylene sorbitanfatty acid ester, polyoxyethylene derivatives of castor oil and ethanol.2. Antimicrobial additive composition according to claim 1 wherein theadditive composition is substantially free of further components. 3.Antimicrobial composition comprising a lactam and a hydrotrope, whereinthe hydrotrope is selected from the group consisting of monopropyleneglycol, dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester,polyoxyethylene derivatives of castor oil and ethanol.
 4. Antimicrobialcomposition comprising an antimicrobial additive composition of claim 1.5. (canceled)
 6. Antimicrobial composition according to claim 1 whereinthe hydrotrope is present at from 0.001 to 5% wt. of the composition. 7.Antimicrobial composition or additive composition according to claim 1wherein the lactam is of formula (I) or (II):

preferably wherein: R1 and R2 are each independently selected from thegroup consisting of hydrogen, halogen, alkyl, cycloalkyl, alkoxy,oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; R3 isselected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl,alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl and—C(O)CR6=CH2; R4 and R5 are independently selected from hydrogen, aryl,heterocyclyl, heteroaryl, and arylalkyl; and R6 is selected fromhydrogen and methyl; and R7 is selected from hydrogen and —C(O)CR6=CH2;and


8. Antimicrobial composition or additive composition according to claim1 wherein the lactam is selected from the group consisting of:5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295),5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310),5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted), methyl2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)(Ref. 309), 5-methylene-4-phenyl-dihydro-pyrrol-2-one (Ref. 219),3-Bromo-4-hexyl-5-(bromomethylene)-2(5H)-furanone (Ref. 113),4-(4-Trifluoromethyl)phenyl)-2(5H)-furanone (Ref. 265),5-Hydroxy-5-methyl-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 313),5-(Thiophenyl-3-methylene)furan-(2H)-one (Ref. 350) and mixturesthereof.
 9. Antimicrobial composition or additive composition accordingto claim 1 wherein the lactam is selected from the group consisting of:5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295),5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310),5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted), methyl2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)(Ref. 309) and mixtures thereof.
 10. Antimicrobial composition oradditive composition according to claim 1 wherein the lactam is presentat from 0.001 to 50% wt. of the composition.
 11. Antimicrobialcomposition or additive composition according to claim 5 wherein thepolyoxyethylene derivative of castor comprises 40 oxyethylene units. 12.Antimicrobial composition or additive composition according to claim 5wherein the polyoxyethylene sorbitan fatty ester comprises from 5 to 80oxyethylene units.
 13. Antimicrobial composition or additive compositionaccording to claim 1 which is a home or personal care composition. 14.Antimicrobial composition or additive composition according to claim 13which is selected from a shampoo, conditioner, deodorant, skin cleansingcomposition, antiperspirant.
 15. Antimicrobial composition or additivecomposition according to claim 13 which is selected from a laundrycomposition, hard surface cleaner and toilet cleaner.
 16. (canceled) 17.Method for making an antimicrobial composition comprising the steps: (i)directly mixing a lactam with a hydrotrope to form an antimicrobialadditive composition; and (ii) mixing the antimicrobial additivecomposition of step (i) with an aqueous carrier.
 18. (canceled) 19.(canceled)
 20. Use of an antimicrobial additive composition orcomposition according to claim 1 for preventing or disrupting microbialgrowth.
 21. (canceled)